Estrogen-sensitive neurons are present in the brain of adult rats with the highest density of estrogen-concentrating cells in the preoptic area, hypothalamus and the amygdala. Estrogen has been found to be concentrated within the cell nucleus. This suggests that the primary mode of action of the hormone might be through the genome. Recently, through the use of inhibitors of RNA and protein synthesis: (1) steroid induced sexual receptivity has been reversibly blocked; (2) the inhibitory effect of a combination of estrogen and progesterone on postcastration LH secretion in vivo has been blocked; (3) the stimulatory effect of estrogen and progesterone on LH release has been blocked. In the studies concerned with sexual behavior the animals were always ovariectomized estrogen-primed females and the inhibitors were administered intracranially. No GTH levels were measured. In the studies concerned with steroid feedback and GTH, the inhibitors were administered subcutaneously with no neural localization. Sexual behavior was not studied. The specific aims of the present proposal are to study the mechanism(s) by which the steroid hormone facilitate sexual receptivity and induce ovulation in the intact cycling rat. Our experimental approach will involve the intracranial infusion of cycloheximide (Cyclo), an inhibitor of protein synthesis, into discrete brain areas implicated in the control of sexual behavior and ovulation. After infusion of Cyclo, we will examine GTH, ovarian steroids, ovulation and sexual receptivity. LH-releasing hormone will be used in an attempt to "override" the effect of the inhibitor. Labelled Cyclo will be infused into discrete brain areas to ascertain the amount of diffusion away from the infusion site. Labelled amino acids will also be used to directly assess intracranial protein synthesis in response to Cyclo into discrete brain areas.